Coxiella burnetii is an obligate intracellular parasite which is generally transmitted from animals to humans. Domestic livestock serve as a reservoir for C. burnetii in most parts of the world, and the disease usually presents as an unapparent infection; in sheep, however, it may lead to late-term abortion. In domestic animals (e.g., sheep, goats and cattle) the disease is shed in urine, feces and placentas, and transmitted either by aerosol or through an intermediate vector (e.g., tick). Further, apparently healthy animals may contain enormous numbers of parasites in placental tissues (Luoto & Huebner, Public Health Rep. 65:541-544, 1950).
Although C. burnetii may be transmitted to humans by ticks, it is usually contracted by inhalation of contaminated dusts and aerosols; contagion between humans is rare. C. burnetii is known to infect many species of animals and birds (Babudieri, Adv. Vet. Sci. 5:81-154, 1959). C. burnetii infection is most common among slaughterhouse employees and farm workers who handle domestic animals or animal products (e.g., wool or hides) (Ormsbee, Ann. Rev. Microbiol. 23:275-292, 1962; Baca & Paretsky, Microbiol. Rev. 47:127-149, 1983).
The acute disease caused by C. burnetii is rarely fatal to humans. The death rate has been estimated at less than 1% among Caucasians, and somewhat higher among indigenous people of equatorial Africa (Ormsbee, Viral and Rickettsial Infections of Man; 4th Ed., ed. F.L. Horsfall Jr. and I. Tamm, pp. 1144-1160, 1985, J. B. Lippincott, Co., Pa.). The incubation period ranges from 1 to 3 weeks, and the disease normally presents as an acute febrile illness. Recovery generally occurs within 1 to 4 weeks, depending on the course of treatment. Occasionally, C. burnetii infection is manifested in other ways, including apparent persistent infection, which can lead to endocarditis or other symptoms in man. The development of chronic endocarditis in humans has previously been thought to arise when a C. burnetii infection is superimposed on a preexisting disease or deformity of the patient, rather than being attributed to a specific property of the pathogen (Peacock et al., Infect. & Immun. 41:1089-1098, 1983; Turck et al., J. Medicine 178:193-217, 1976; Tobin et al., Amer. J. Med. 72:396-399, 1982; Robson et al., British Med. J. 2:980-983, 1959). Comparative analyses of infected sera and of the biological properties of microorganisms isolated from various sequelae of C. burnetii infection (acute disease, chronic endocarditis, abortion, etc.) have not indicated that specific C. burnetii variants produce a particular manifestation. Comparative analyses have, however, demonstrated antigenic variation in C. burnetii (Stoker & Fiset, Can. J. Microbiol. 2:310-321, 1956). This antigenic phase variation is characterized primarily by the reactivity of different isolates with hyperimmune sera against a phase I or phase II Nine Mile strain of C. burnetii. However, this phenotypic variation cannot be used to predict sequelae of C. burnetii infection.
Differentiation of C. burnetii caused symptoms from influenza, primary atypical pneumonia, bacterial pneumonia, or a number of other types of pneumonia and flu-like symptoms caused by a variety of etiological agents is a slow and difficult process. It is also difficult to differentiate C. burnetii-induced hepatitis from infectious or idiopathic hepatitis. Present differentiation procedures require isolation of C. burnetii from tissues or blood, and subsequent culture in embryonated eggs or in guinea pigs. An alternative method for differentiation requires demonstration of a significant rise in specific anti-C. burnetii antibody titer in successive serum samples. Isolation of C. burnetii is highly hazardous, and is inadvisable in the absence of adequate (P-3) isolation facilities. Even then, safety procedures must be rigidly followed to avoid contamination. In addition, confirmation of findings usually takes 2 to 3 weeks. Serological methods, while simpler and safer than culturing, also require considerable time (usually 3 weeks) to confirm the diagnosis, and are therefore of little use to a practicing physician, who usually prefers to start treatment within 24 hours. In addition to being costly and time-consuming, both techniques require highly specialized facilities, equipment, and reagents that are generally available only in special laboratories. Furthermore, serological diagnosis of chronic C. burnetii infections would be difficult since the appropriate (pre-immune) serum sample necessary for a definitive diagnosis would not be available.
Due to these difficulties in diagnosis, it is hard to accurately estimate the prevalence of C. burnetii infection throughout the world. Furthermore, there has been no way to predict from the initial symptoms the result of the infection, i.e., whether it will result in a persistent infection, including hepatitis and/or chronic endocarditis, or in acute disease symptoms. Such differential diagnosis is important for a number of reasons. For example, the prognosis for infections caused by acute disease strains is quite good. While debilitating symptoms may result if left untreated, appropriate treatment (with tetracyclines, for example) results in a rapid cure of the malady. However, it is important to specifically diagnose acute disease caused by C. burnetii infections because tetracycline is not the antibiotic of choice for treatment of most acute disease symptoms, such as pneumonias, fevers or other flu-like symptoms. It is also important to diagnose disease caused by chronic strains of C. burnetii due to the risk of developing complications that are usually fatal. There is currently no known cure for these chronic infections. Finally, it is important to be able to determine which animals harbor C. burnetii and to be able to determine if certain species, or herds, are serving as natural reservoirs for chronic disease-causing strains which may infect humans.
Accordingly, there exists a need in the art for a rapid, sensitive, and simple method for the detection of C. burnetii in biological samples. In addition, a method for distinguishing C. burnetii strains capable of causing chronic disease from those associated only with acute infection would be useful for determining optimal patient treatment. The present invention fulfills these needs and further provides other related advantages.